7. Paroxysmal Nocturnal Hemoglobinuria (PNH) | USMLE Step 1 Pathology

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Paroxysmal Nocturnal Hemoglobinuria (PNH): USMLE Step 1 Pathology

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder characterized by the abnormal expansion of a clone of hematopoietic cells deficient in glycosylphosphatidylinositol (GPI)-anchored proteins, particularly CD55 and CD59. 💉 These proteins normally protect red blood cells (RBCs) from complement-mediated destruction. In PNH, deficiency of these proteins renders RBCs susceptible to complement-mediated hemolysis, leading to episodes of hemoglobinuria, particularly during periods of reduced pH such as at night or during infections. Clinical manifestations include hemolytic anemia, thrombosis, and bone marrow failure. Diagnosis involves flow cytometry to detect deficient GPI-anchored proteins on RBCs, granulocytes, and monocytes. Treatment includes supportive measures such as blood transfusions, anticoagulation for thrombotic events, and targeted therapies such as eculizumab, a monoclonal antibody against complement protein C5. Understanding the pathophysiology, clinical features, and management of PNH is crucial for medical students preparing for the USMLE Step 1 exam.

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